The Diagnostic Accuracy of First-Year Ophthalmology Residents on Call: Considerations for Postgraduate Year 2 (PGY-2) Standardizations of Call Structure.

Background Ophthalmology is a unique specialty with limited exposure during medical school. To improve the transition to ophthalmology residency, the Accreditation Council for Graduate Medical Education (ACGME) announced in 2017 that all ophthalmology residency programs would move to a combined post-graduate year (PGY) 1 year with mandatory integration by 2023. Currently, there are no standardized guidelines from the American Board of Ophthalmology (ABO) or the Accreditation Council for Graduate Medical Education (ACGME) to address ophthalmology resident competence prior to becoming the primary contact for inpatient and emergency room (ER) consultations as a PGY-2. Novice residents may not be equipped to accurately diagnose vision or life-threatening ocular conditions. A balance between resident autonomy and supervision is required for proper training without increasing patient morbidity and mortality. Objective This study's objective is to examine the diagnostic accuracy of PGY-2 ophthalmology non-integrated residents on call to standardize supervision requirements (through buddy-call) prior to initiating indirectly supervised calls. Methods All inpatient and ER ophthalmology consults for the first seven weeks of the year evaluated by PGY-2 (junior) residents were supervised and graded as "correct" or "incorrect" by PGY-4 (senior) residents. Results One hundred forty-eight consults were seen over 30 call days over a period of seven weeks (4.93 consults per call). The percentage of correct diagnoses increased with each successive week (R2 = 0.9581; correlation = 0.979). The greatest percent increase of correctly diagnosed encounters was between weeks 2 and 3 (19.14%) correlating to call numbers 10-16 and 45-68 patient encounters. The mean percent accuracy surpassed 70% during weeks 3-4, and improvement continued to week 7. High-acuity diagnoses were identified consistently 100% of the time from week 5 onward. Conclusion Our analysis indicated that diagnostic accuracy was greater than 70% between weeks 3 and 4 with high-acuity diagnostic accuracy reaching 100% at week 5. It can be postulated that optimal direct senior resident supervision is needed for at least 3-5 weeks before transitioning to indirectly supervised calls by PGY-2 residents. This standardization would allow junior residents to acquire sufficient clinical experience to accurately make a diagnosis and prevent patient morbidity. Further research nationally is necessary prior to creating a standardized call structure for PGY-2 residents especially with the newly mandatory integrated ophthalmology residency programs.

The Role of the Microbiome in First Episode of Psychosis.

The relationship between the gut-brain-microbiome axis has gained great importance in the study of psychiatric disorders, as it may represent a new target for their treatment. To date, the available literature suggests that the microbiota may influence the pathophysiology of several diseases, including psychosis. The aim of this review is to summarize the clinical and preclinical studies that have evaluated the differences in microbiota as well as the metabolic consequences related to psychosis. Current data suggest that the genera Lactobacillus and Megasphaera are increased in schizophrenia (SZ), as well as alterations in the glutamate-glutamine-GABA cycle, serum levels of tryptophan, kynurenic acid (KYNA), and short-chain fatty acids (SCFAs). There are still very few studies on early-onset psychosis, thus more studies are needed to be able to propose targeted therapies for a point when the disease has just started or has not yet progressed.

Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes.

Long-term studies have shown significantly lower mortality rates in patients with continuous clozapine (CLZ) treatment than other antipsychotics. We aimed to evaluate epigenetic age and DNA methylome differences between CLZ-treated patients and those without psychopharmacological treatment. The DNA methylome was analyzed using the Infinium MethylationEPIC BeadChip in 31 CLZ-treated patients with psychotic disorders and 56 patients with psychiatric disorders naive to psychopharmacological treatment. Delta age (Δage) was calculated as the difference between predicted epigenetic age and chronological age. CLZ-treated patients were stratified by sex, age, and years of treatment. Differential methylation sites between both groups were determined using linear regression models. The Δage in CLZ-treated patients was on average lower compared with drug-naive patients for the three clocks analyzed; however, after data-stratification, this difference remained only in male patients. Additional differences were observed in Hannum and Horvath clocks when comparing chronological age and years of CLZ treatment. We identified 44,716 differentially methylated sites, of which 87.7% were hypomethylated in CLZ-treated patients, and enriched in the longevity pathway genes. Moreover, by protein-protein interaction, AMPK and insulin signaling pathways were found enriched. CLZ could promote a lower Δage in individuals with long-term treatment and modify the DNA methylome of the longevity-regulating pathways genes.

Genome-Wide Analysis of Disordered Eating Behavior in the Mexican Population.

Alterations in eating behavior characterized eating disorders (ED). The genetic factors shared between ED diagnoses have been underexplored. The present study performed a genome-wide association study in individuals with disordered eating behaviors in the Mexican population, blood methylation quantitative trait loci (blood-meQTL), summary data-based Mendelian randomization (SMR) analysis, and in silico function prediction by different algorithms. The analysis included a total of 1803 individuals. We performed a genome-wide association study and blood-meQTL analysis by logistic and linear regression. In addition, we analyzed in silico functional variant prediction, phenome-wide, and multi-tissue expression quantitative trait loci. The genome-wide association study identified 44 single-nucleotide polymorphisms (SNP) associated at a nominal value and seven blood-meQTL at a genome-wide threshold. The SNPs show enrichment in genome-wide associations of the metabolic and immunologic domains. In the in silico analysis, the SNP rs10419198 (p-value = 4.85 × 10-5) located on an enhancer mark could change the expression of PRR12 in blood, adipocytes, and brain areas that regulate food intake. Additionally, we found an association of DNA methylation levels of SETBP1 (p-value = 6.76 × 10-4) and SEMG1 (p-value = 5.73 × 10-4) by SMR analysis. The present study supports the previous associations of genetic variation in the metabolic domain with ED.

Patient Characteristics Associated With the Need for Long-Term Treatment in a Child Psychiatry Hospital After the Earthquake in Mexico City.

OBJECTIVE: The aim of this study is to determine the demographic and clinical characteristics associated with the need for long-term treatment in a child psychiatry facility. METHOD: Demographic characteristics, diagnosis, source of referral, time elapsed between the earthquake and the request for care, and the treatment prescribed in the baseline assessment were compared between a group of subjects that required long-term treatment (LTT) and a group that was discharged after a brief intervention (D). RESULTS: A total of 171 patients were seen, and 27% of the subjects required LTT. In general, these subjects were younger, referred from highly affected areas, presented a delay in seeking care, and were mainly diagnosed with anxiety and stress-related disorders. CONCLUSIONS: These findings suggest the need for research regarding the design of mental health programs for the early detection of psychopathology after natural disasters in children and adolescents.

Association study of Catechol-O-Methyltransferase (COMT) rs4680 Val158Met gene polymorphism and suicide attempt in Mexican adolescents with major depressive disorder.

AIM: We analyzed the association between SLC6A4, DRD2, COMT and MAOA genes and suicide attempt (SA) in Mexican adolescent patients with major depressive disorder (MDD). METHODS: The sample included 197 adolescents (127 females and 70 males) with principal diagnosis of MDD. Among them, 63 patients had SA at least once and 134 had not SA. The mean age of patients with and without SA was 15 ± 1.4 and 14 ± 1.5 years, respectively. We analyzed the genotype and allele distribution between patients with and without SA of SLC6A4 (5HTTLPR/rs25531), DRD2 (rs6275), COMT (rs4680), and MAOA (uVNTR). RESULTS: We did not find genotype or allele association between SA and SLC6A4 (χ2=0.67, p = 0.71; χ2=0.07, p = 0.77, respectively), DRD2 (χ2=0.05, p = 0.97; χ2=0.003, p = 0.95), and MAOA (females: χ2=0.86, p = 0.64; χ2=0, p = 1/males: χ2=0.008, p = 0.92) genes. However, there were differences in genotype frequencies of COMT/rs4680 between patients with SA and without SA (χ2=11.17, p = 0.003). Also, we observed a high frequency of Met158 allele showing an increased risk of having presented at least one SA (χ2=10.6, p = 0.001; OR = 1.43; 95% CI, 1.17-1.74). CONCLUSIONS: Our findings showed an association between low activity genotype and allele of Val158Met polymorphism of COMT gene and SA in Mexican adolescents with MDD.

Association Study among Comethylation Modules, Genetic Polymorphisms and Clinical Features in Mexican Teenagers with Eating Disorders: Preliminary Results.

Eating disorders are psychiatric disorders characterized by disturbed eating behaviors. They have a complex etiology in which genetic and environmental factors interact. Analyzing gene-environment interactions could help us to identify the mechanisms involved in the etiology of such conditions. For example, comethylation module analysis could detect the small effects of epigenetic interactions, reflecting the influence of environmental factors. We used MethylationEPIC and Psycharray microarrays to determine DNA methylation levels and genotype from 63 teenagers with eating disorders. We identified 11 comethylation modules in WGCNA (Weighted Gene Correlation Network Analysis) and correlated them with single nucleotide polymorphisms (SNP) and clinical features in our subjects. Two comethylation modules correlated with clinical features (BMI and height) in our sample and with SNPs associated with these phenotypes. One of these comethylation modules (yellow) correlated with BMI and rs10494217 polymorphism (associated with waist-hip ratio). Another module (black) was correlated with height, rs9349206, rs11761528, and rs17726787 SNPs; these polymorphisms were associated with height in previous GWAS. Our data suggest that genetic variations could alter epigenetics, and that these perturbations could be reflected as variations in clinical features.

Individuals Diagnosed with Binge-Eating Disorder Have DNA Hypomethylated Sites in Genes of the Metabolic System: A Pilot Study.

Binge-eating disorder, recently accepted as a diagnostic category, is differentiated from bulimia nervosa in that the former shows the presence of binge-eating episodes and the absence of compensatory behavior. Epigenetics is a conjunct of mechanisms (like DNA methylation) that regulate gene expression, which are dependent on environmental changes. Analysis of DNA methylation in eating disorders shows that it is reduced. The present study aimed to analyze the genome-wide DNA methylation differences between individuals diagnosed with BED and BN. A total of 46 individuals were analyzed using the Infinium Methylation EPIC array. We found 11 differentially methylated sites between BED- and BN-diagnosed individuals, with genome-wide significance. Most of the associations were found in genes related to metabolic processes (ST3GAL4, PRKAG2, and FRK), which are hypomethylated genes in BED. Cg04781532, located in the body of the PRKAG2 gene (protein kinase AMP-activated non-catalytic subunit gamma 2), was hypomethylated in individuals with BED. Agonists of PRKAG2, which is the subunit of AMPK (AMP-activated protein kinase), are proposed to treat obesity, BED, and BN. The present study contributes important insights into the effect that BED could have on PRKAG2 activation.

Psychiatric Comorbidity in Mexican Adolescents with a Diagnosis of Eating Disorders Its Relationship with the Body Mass Index.

The prevalence of comorbid psychiatric disorders among patients with eating disorders (ED) is higher than the general population. Individuals diagnosed with eating disorders have changes in their body mass index which could promote severe metabolic disruptions. This study aimed (1) to report the prevalence of comorbid psychiatric disorders among a Mexican adolescent sample diagnosed with eating disorders, (2) to compare our results with the prevalence of psychiatric disorders reported from a national survey of mental health of adolescents, (3) to compare the presence of psychiatric comorbidities between ED diagnoses, and (4) to explore the relationship of these comorbidities with the body mass index. In the study, we included 187 Mexican adolescents diagnosed with eating disorders. The psychiatric comorbidities were evaluated using the Mini International Neuropsychiatric Interview for children/adolescents, and a revised questionnaire on eating and weight patterns. We found that 89% of the Mexican adolescents diagnosed with ED had another psychiatric comorbidity. Major depressive disorder (52.40%) and suicide risk (40%) were the most prevalent comorbidities. Attention and deficit hyperactivity disorder (ADHD) prevalence was different between ED diagnosis, and adolescents with binge-eating disorder and ADHD had the higher body mass index. Our results showed that in this sample of Mexican adolescents, the presence of comorbidities could impact body mass index. This emphasizes the importance that clinicians take into consideration the presence of psychiatric comorbidities to achieve an integrative treatment for adolescents diagnosed with ED.

Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals.

The combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p < 5.00e-05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.

High polygenic burden is associated with blood DNA methylation changes in individuals with suicidal behavior.

Suicidal behavior is result of the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide). Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. We identified 153 differentially methylated sites between individuals with low and high-PRS. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment (CHD7, RFX4, KCNA1, PLCB1, PITX1, NUMBL) and ATP binding (KIF7, NUBP2, KIF6, ATP8B1, ATP11A, CLCN7, MYLK, MAP2K5). Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.

Gene-level genome-wide association analysis of suicide attempt, a preliminary study in a psychiatric Mexican population.

BACKGROUND: Evidence suggests that liability for suicide behavior is heritable; additionally, suicide has been partly related to other psychiatric disorders. Nevertheless, most of the information reported so far address Caucasian and Asian individuals. Hence, our aim was to conduct a gene-level association study in Mexican psychiatric individuals diagnosed with suicide attempt. METHODS: We recruited 192 individuals from two clinical centers in Mexico. All participants were born in Mexico and had Mexican parents and grandparents. Direct genotyping was performed using the commercial platform Infinium PsychArray BeadChip. A p-value lower than 1e-05 was considered as gene-level significant and a p-value lower than 1e-04 was considered as gene-level nominal significant. RESULTS: Our analyses showed that SCARA5 was associated to suicide intent at a gene-level with statistical significance (p-value = 1.12e-6). Other genes were nominally associated with suicide attempt: GHSR (p-value = 0.0004), RGS10 (p-value = 5.13e-5), and STK33 (p-value = 3.62e-5). Regarding gene variant analyses, the SNPs with a statistical association (p > .05) were rs561361616, rs1537577, rs11198999 for RGS10, and rs11041981, rs11041993, rs11041994, rs11041995, rs11041997, rs10840083, rs10769918 for STK33. For these genes, previous studies have associated SCARA5 with depression, GHSR with alcohol dependence and depression, and RGS10 with schizophrenia and depression. To date, STK33 has not been associated with any psychiatric disorder. CONCLUSION: Our outcomes revealed that SCARA5, GHSR, RGS10 and STK33 could be considered as risk biomarkers for suicide attempt behavior in our Mexican psychiatric sample. We recommend to perform larger scale analyses to have conclusive results.

Genome-wide association study of suicide attempt in a Mexican population: a study protocol.

INTRODUCTION: Suicidality is a complex behaviour and a major health problem; the specific features that could predispose to suicidal behaviour have been extensively investigated, most frequently in European and Asian populations. Therefore, our aim is to present a protocol that will explore suicide attempt in Mexican individuals diagnosed with psychiatric disorders, through a genome-wide association study (GWAS). METHOD AND ANALYSIS: We will perform a GWAS by comparing 700 individuals who have suicide attempt history, with control subjects without suicide attempt history (n=500). The genotyping will be conducted using the Infinium PsychArray BeadChip and quality controls will be applied to single nucleotides (SNPs) genotyped. After that, we will perform the imputation using reference panels provided by the Haplotype Reference Consortium. We will perform two different workflows: (A) the classic GWAS analysis applying the same weight to all the variants and (B) an algorithm with prediction of deleteriousness of variants. ETHICS AND DISSEMINATION: This study was approved by the ethics and investigation committees of the National Institute of Genomic Medicine on 22 July 2015, No CEI 215/13. We plan to disseminate research findings in scientific conferences and as a manuscript in peer-reviewed journals. TRIAL REGISTRATION NUMBER: CEI 215/13.

Effectiveness of a treatment guideline for schizophrenia in adolescents: Lessons from a middle-income country.

INTRODUCTION: Treatment guidelines for schizophrenia represent a standard way to manage patients, especially in countries with limited staff resources. However, they have not been compared on their efficacy with treatment as usual, despite adult studies suggesting they can be more effective. METHODS: Inpatient and outpatient adolescents with schizophrenia were randomly allocated to be either treated according to a guideline-based treatment ( n = 43) or treatment as usual ( n = 44). The effects on symptoms, psychosocial functioning and cognition were compared in a 6-month follow-up. RESULTS: There were no differences between groups in the pharmacological treatment, reduction in symptom severity or cognition. The guideline-based treatment group showed a better functioning at months 3 and 6. CONCLUSION: The guideline-based treatment had a greater effect than the treatment as usual in the psychosocial functioning of adolescent patients ( www.clinicaltrials.gov ; II3/02/0811).

Association between Polymorphisms of the DRD2 and ANKK1 Genes and Suicide Attempt: A Preliminary Case-Control Study in a Mexican Population.

BACKGROUND: The aim of this study was to analyze the possible association of polymorphic variants of the DRD2 and ANKK1 genes with suicide attempt in a Mexican population. METHODS: We conducted a case-control study in 289 subjects (166 suicide attempters and 123 healthy controls). We genotyped 2 polymorphisms of DRD2 (rs6275 and rs1799978) and 1 polymorphism of ANKK1 (rs1800497); then we analyzed the association between suicide attempt and these polymorphisms through genotypes, alleles, and inheritance models. RESULTS: Individuals who carried the TT genotype of the rs1800497 showed a 3-fold risk of attempting suicide (OR = 3.01; 95% CI 1.56-5.81, p = 0.001) when evaluated through the recessive model. In an analysis stratified by gender, this risk factor remained present among females (OR = 2.81; 95% CI 1.37-5.75) as well as males (OR = 3.3; 95% CI 1.01-10.77). CONCLUSION: Our results suggest that the rs1800497 variant of the ANKK1 gene could increase the risk of suicide attempt in a Mexican population. However, further studies using larger samples are necessary to obtain more conclusive results.

Validation of the Impulsive/Premeditated Aggression Scale in Mexican psychiatric patients.

INTRODUCTION: Aggression has been linked to several psychiatric disorders. None of the available instruments validated in Mexico is able to classify aggression as impulsive or premeditated. The Impulsive/Premeditated Aggression Scale (IPAS) is a self-report instrument designed to characterize aggressiveness as predominately impulsive or premeditated. OBJECTIVE: The aim of the study was to determine the validity and reliability of the IPAS in a sample of Mexican psychiatric patients. METHOD: A total of 163 patients diagnosed with affective, anxiety or psychotic disorder were included. A principal-component factor analysis was performed to obtain construct validity of the IPAS impulsive and premeditated aggression subscales; convergent validity as well as internal consistency of subscales were also determined. RESULTS: The rotated matrix accounted for 33.4% of the variance. Significant values were obtained for convergent validity and reliability of the IPAS subscales. CONCLUSION: The IPAS is an adequate instrument, which might be used to differentiate the type of aggressive behavior in Mexican psychiatric patients.

Exploring personality features in patients with affective disorders and history of suicide attempts: a comparative study with their parents and control subjects.

Personality traits are important candidate predictors of suicidal behavior. Several studies have reported an association between personality/temperament traits and suicidal behavior, suggesting personality traits as intermediary phenotypes related to suicidal behavior. Thus, it is possible that suicide attempts can be accounted for by increased familial rates of risk personality traits. The aim of this work was to evaluate personality traits in affective disorder patients with attempted suicide and to compare them with the personality trait scores of their parents. In addition, ITC scores in the two groups were compared with a healthy control sample. The patients evaluated met the DSM-IV criteria for major depression disorder or dysthymia and had a documented history of suicide attempts. Psychiatric diagnoses of patients and parents were done according to the SCID-I and the personality was assessed using the Temperament and Character Inventory. We analyzed 49 suicide attempt subjects and their parents (n = 95) and 89 control subjects. We observed that temperament and character dimensions were similar between patients and their parents (P > 0.05). In particular, we observed that high HA and low P, SD, and CO were shared among families. Our study is the first to report that the personality traits of affective disorder patients with a history of attempted suicide are shared between patients and their parents.